Search results for: optimal gripper design
8750 Physiological Response of Water-Restricted Xhosa Goats Supplemented with Vitamin C
Authors: O.F. Akinmoladun, F.N. Fon, C.T. Mpendulo, O. Okoh
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The sustainability of livestock production is under threat as a result of water scarcity, fluctuating precipitation, and high environmental temperature. These combined stressors have impacted negatively on general animal production and welfare, necessitating a very reliable and cost-effective management practices, especially in arid and water-limited regions of the world. Instead of the above, this study was designed to investigate the growth performance and physiological response of water-restricted Xhosa ear-lobe goats fed diets supplemented with single or multiple vitamin C (VC) during summer. The total forty-eight goats used for the experiment were balanced for body weight and randomly assigned to the seven treatment groups (seven goats/treatment): GI (W100%); GII (W70%); GIII (W50%); GIV (W70%+3g/day VC); GV ((W50% +3g/day VC); GVI (W70%+3g/d VC+extra 5g on every eight-day); GVII (W50%+3g/d VC+extra 5g on every eight-day). The design was a complete randomized design and VC was administered per os. At the end of the 75-day feeding trial, GIII (W50%) animals were the most affected (P<0.05) and the effect was more pronounced in their body condition scores (BCs). Weight loss and depression in feed intake due to water restriction (P<0.05) were attenuated by VC treated groups (GIV-GVII). Changes in body thermal gradient (BTG) and rectal temperature (RcT) were similar (P>0.05) across the various experimental groups. The attenuation effect of VC was significant in responses to respiratory rate (RR) and cortisol. Supplementation of VC (either single or multiple) did not significantly (P>0.05) improve water restriction effect on body condition scores (BCs) and FAMACHA©. The current study found out that Xhosa ear lobe goats can adapt to the prevailing bioclimatic changes and limited water intake. However, supplementation of vitamin C can be beneficial at modulating these stressful stimuli. Continuous consistencies in the outcome of vitamin C on water-stressed animals can help validate recommendations especially to farmers in the arid and water-limited regions across the globe.Keywords: vitamin C, Xhosa ear-lobe, thermotolerance, water stress
Procedia PDF Downloads 1358749 Drawing Building Blocks in Existing Neighborhoods: An Automated Pilot Tool for an Initial Approach Using GIS and Python
Authors: Konstantinos Pikos, Dimitrios Kaimaris
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Although designing building blocks is a procedure used by many planners around the world, there isn’t an automated tool that will help planners and designers achieve their goals with lesser effort. The difficulty of the subject lies in the repeating process of manually drawing lines, while not only it is mandatory to maintain the desirable offset but to also achieve a lesser impact to the existing building stock. In this paper, using Geographical Information Systems (GIS) and the Python programming language, an automated tool integrated into ArcGIS PRO, is being presented. Despite its simplistic enviroment and the lack of specialized building legislation due to the complex state of the field, a planner who is aware of such technical information can use the tool to draw an initial approach of the final building blocks in an area with pre-existing buildings in an attempt to organize the usually sprawling suburbs of a city or any continuously developing area. The tool uses ESRI’s ArcPy library to handle the spatial data, while interactions with the user is made throught Tkinter. The main process consists of a modification of building edgescoordinates, using NumPy library, in an effort to draw the line of best fit, so the user can get the optimal results per block’s side. Finally, after the tool runs successfully, a table of primary planning information is shown, such as the area of the building block and its coverage rate. Regardless of the primary stage of the tool’s development, it is a solid base where potential planners with programming skills could invest, so they can make the tool adapt to their individual needs. An example of the entire procedure in a test area is provided, highlighting both the strengths and weaknesses of the final results.Keywords: arcPy, GIS, python, building blocks
Procedia PDF Downloads 1858748 Efficient L-Xylulose Production Using Whole-Cell Biocatalyst With NAD+ Regeneration System Through Co-Expression of Xylitol Dehydrogenase and NADH Oxidase in Escherichia Coli
Authors: Mesfin Angaw Tesfay
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L-Xylulose is a potentially valuable rare sugar used as starting material for antiviral and anticancer drug development in pharmaceutical industries. L-Xylulose exist in a very low concentration in nature and have to be synthesized from cheap starting materials such as xylitol through biotechnological approaches. In this study, cofactor engineering and deep eutectic solvent were applied to improve the efficiency of L-xylulose production from xylitol. A water-forming NAD+ regeneration enzyme (NADH oxidase) from Streptococcus mutans ATCC 25175 was introduced into E. coli with xylitol-4-dehydrogenase (XDH) of Pantoea ananatis resulting in recombinant cells harboring the vector pETDuet-xdh-SmNox. Further, three deep eutectic solvents (DES) including, Choline chloride/glycerol (ChCl/G), Choline chloride/urea (ChCl/U), and Choline chloride/ethylene glycol (ChCl/EG) have been employed to facilitate the conversion efficiency of L-xylulose from xylitol. The co-expression system exhibited optimal activity at a temperature of 37 ℃ and pH 8.5, and the addition of Mg2+ enhanced the catalytic activity by 1.19-fold. Co-expression of NADH oxidase with XDH enzyme resulted in increased L-xylulose concentration and productivity from xylitol as well as the intracellular NAD+ concentration. Two of the DES used (ChCl/U and ChCl/EG) show positive effects on product yield and the ChCl/G has inhibiting effects. The optimum concentration of ChCl/U was 2.5%, which increased the L-xylulose yields compared to the control without DES. In a 1 L fermenter the final concentration and productivity of L-xylulose from 50 g/L of xylitol reached 48.45 g/L, and 2.42 g/L.h respectively, which was the highest report. Overall, this study is a suitable approach for large-scale production of L-xylulose from xylitol using the engineered E. coli cell.Keywords: Xylitol-4-dehydrogenase, NADH oxidase, L-xylulose, Xylitol, Coexpression, DESs
Procedia PDF Downloads 308747 An Experimental Investigation of the Surface Pressure on Flat Plates in Turbulent Boundary Layers
Authors: Azadeh Jafari, Farzin Ghanadi, Matthew J. Emes, Maziar Arjomandi, Benjamin S. Cazzolato
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The turbulence within the atmospheric boundary layer induces highly unsteady aerodynamic loads on structures. These loads, if not accounted for in the design process, will lead to structural failure and are therefore important for the design of the structures. For an accurate prediction of wind loads, understanding the correlation between atmospheric turbulence and the aerodynamic loads is necessary. The aim of this study is to investigate the effect of turbulence within the atmospheric boundary layer on the surface pressure on a flat plate over a wide range of turbulence intensities and integral length scales. The flat plate is chosen as a fundamental geometry which represents structures such as solar panels and billboards. Experiments were conducted at the University of Adelaide large-scale wind tunnel. Two wind tunnel boundary layers with different intensities and length scales of turbulence were generated using two sets of spires with different dimensions and a fetch of roughness elements. Average longitudinal turbulence intensities of 13% and 26% were achieved in each boundary layer, and the longitudinal integral length scale within the three boundary layers was between 0.4 m and 1.22 m. The pressure distributions on a square flat plate at different elevation angles between 30° and 90° were measured within the two boundary layers with different turbulence intensities and integral length scales. It was found that the peak pressure coefficient on the flat plate increased with increasing turbulence intensity and integral length scale. For example, the peak pressure coefficient on a flat plate elevated at 90° increased from 1.2 to 3 with increasing turbulence intensity from 13% to 26%. Furthermore, both the mean and the peak pressure distribution on the flat plates varied with turbulence intensity and length scale. The results of this study can be used to provide a more accurate estimation of the unsteady wind loads on structures such as buildings and solar panels.Keywords: atmospheric boundary layer, flat plate, pressure coefficient, turbulence
Procedia PDF Downloads 1438746 Cost Overrun in Construction Projects
Authors: Hailu Kebede Bekele
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Construction delays are suitable where project events occur at a certain time expected due to causes related to the client, consultant, and contractor. Delay is the major cause of the cost overrun that leads to the poor efficiency of the project. The cost difference between completion and the originally estimated is known as cost overrun. The common ways of cost overruns are not simple issues that can be neglected, but more attention should be given to prevent the organization from being devastated to be failed, and financial expenses to be extended. The reasons that may raised in different studies show that the problem may arise in construction projects due to errors in budgeting, lack of favorable weather conditions, inefficient machinery, and the availability of extravagance. The study is focused on the pace of mega projects that can have a significant change in the cost overrun calculation.15 mega projects are identified to study the problem of the cost overrun in the site. The contractor, consultant, and client are the principal stakeholders in the mega projects. 20 people from each sector were selected to participate in the investigation of the current mega construction project. The main objective of the study on the construction cost overrun is to prioritize the major causes of the cost overrun problem. The methodology that was employed in the construction cost overrun is the qualitative methodology that mostly rates the causes of construction project cost overrun. Interviews, open-ended and closed-ended questions group discussions, and rating qualitative methods are the best methodologies to study construction projects overrun. The result shows that design mistakes, lack of labor, payment delay, old equipment and scheduling, weather conditions, lack of skilled labor, payment delays, transportation, inflation, and order variations, market price fluctuation, and people's thoughts and philosophies, the prior cause of the cost overrun that fail the project performance. The institute shall follow the scheduled activities to bring a positive forward in the project life.Keywords: cost overrun, delay, mega projects, design
Procedia PDF Downloads 668745 Engineered Bio-Coal from Pressed Seed Cake for Removal of 2, 4, 6-Trichlorophenol with Parametric Optimization Using Box–Behnken Method
Authors: Harsha Nagar, Vineet Aniya, Alka Kumari, Satyavathi B.
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In the present study, engineered bio-coal was produced from pressed seed cake, which otherwise is non-edible in origin. The production process involves a slow pyrolysis wherein, based on the optimization of process parameters; a substantial reduction in H/C and O/C of 77% was achieved with respect to the original ratio of 1.67 and 0.8, respectively. The bio-coal, so the product was found to have a higher heating value of 29899 kJ/kg with surface area 17 m²/g and pore volume of 0.002 cc/g. The functional characterization of bio-coal and its subsequent modification was carried out to enhance its active sites, which were further used as an adsorbent material for removal of 2,4,6-Trichlorophenol (2,4,6-TCP) herbicide from the aqueous stream. The point of zero charge for the bio-coal was found to be pH < 3 where its surface is positively charged and attracts anions resulting in the maximum 2, 4, 6-TCP adsorption at pH 2.0. The parametric optimization of the adsorption process was studied based on the Box-Behken design with the desirability approach. The results showed optimum values of adsorption efficiency of 74.04% and uptake capacity of 118.336 mg/g for an initial metal concentration of 250 mg/l and particle size of 0.12 mm at pH 2.0 and 1 g/L of bio-coal loading. Negative Gibbs free energy change values indicated the feasibility of 2,4,6-TCP adsorption on biochar. Decreasing the ΔG values with the rise in temperature indicated high favourability at low temperatures. The equilibrium modeling results showed that both isotherms (Langmuir and Freundlich) accurately predicted the equilibrium data, which may be attributed to the different affinity of the functional groups of bio-coal for 2,4,6-TCP removal. The possible mechanism for 2,4,6-TCP adsorption is found to be physisorption (pore diffusion, p*_p electron donor-acceptor interaction, H-bonding, and van der Waals dispersion forces) and chemisorption (phenolic and amine groups chemical bonding) based on the kinetics data modeling.Keywords: engineered biocoal, 2, 4, 6-trichlorophenol, box behnken design, biosorption
Procedia PDF Downloads 1218744 Produced Water Treatment Using Novel Solid Scale Inhibitors Based on Silver Tungstate Loaded Kit-6: Static and Modeling Evaluation
Authors: R. Hosny, Mahmoud F. Mubarak, Heba M. Salem, Asmaa A. Abdelrahman
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Oilfield scaling is a major problem in the oil and gas industry. Scale issues cost the industry millions of dollars in damage and lost production every year. One of the main causes of global production decline is scale. In this study, solid scale inhibitors based on silver tungstate loaded KIT-6 were synthesized and evaluated in both static and scale inhibition modeling. The silver tungstate loaded KIT-6 catalysts were synthesized via a simple impregnated method using 3D mesoporous KIT-6 as support. The synthesized materials were characterized using wide and low XRD, N2 adsorption–desorption analysis, TGA analysis, and FTIR, SEM, and XPS analysis. The scale inhibition efficiency of the synthesized materials was evaluated using a static scale inhibition test. The results of this study demonstrate the potential application of silver tungstate-loaded KIT-6 solid scale inhibitors for the oil and gas industry. The results of this study will contribute to the development of new and innovative solid scale inhibitors based on silver tungstate-loaded KIT-6. The inhibition efficiency of the scale inhibitor increases, and calcite scale inhibitor decreases with increasing pH (2 to8), it proposes that the scale inhibitor was more effective under alkaline conditions. An inhibition efficiency of 99% on calcium carbonate can be achieved at the optimal dosage of 7.5 ppm at 55oC, indicating that the scale inhibitor exhibits a relatively good inhibition performance on calcium carbonate. The use of these materials can potentially lead to more efficient and cost-effective solutions for scaling inhibition in various industrial processes.Keywords: produced water treatment, solid scale inhibitors, calcite, silver tungestate, 3 D mesoporous KIT-6, oilfield scales, adsorption
Procedia PDF Downloads 1488743 Human Factors Integration of Chemical, Biological, Radiological and Nuclear Response: Systems and Technologies
Authors: Graham Hancox, Saydia Razak, Sue Hignett, Jo Barnes, Jyri Silmari, Florian Kading
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In the event of a Chemical, Biological, Radiological and Nuclear (CBRN) incident rapidly gaining, situational awareness is of paramount importance and advanced technologies have an important role to play in improving detection, identification, monitoring (DIM) and patient tracking. Understanding how these advanced technologies can fit into current response systems is essential to ensure they are optimally designed, usable and meet end-users’ needs. For this reason, Human Factors (Ergonomics) methods have been used within an EU Horizon 2020 project (TOXI-Triage) to firstly describe (map) the hierarchical structure in a CBRN response with adapted Accident Map (AcciMap) methodology. Secondly, Hierarchical Task Analysis (HTA) has been used to describe and review the sequence of steps (sub-tasks) in a CBRN scenario response as a task system. HTA methodology was then used to map one advanced technology, ‘Tag and Trace’, which tags an element (people, sample and equipment) with a Near Field Communication (NFC) chip in the Hot Zone to allow tracing of (monitoring), for example casualty progress through the response. This HTA mapping of the Tag and Trace system showed how the provider envisaged the technology being used, allowing for review and fit with the current CBRN response systems. These methodologies have been found to be very effective in promoting and supporting a dialogue between end-users and technology providers. The Human Factors methods have given clear diagrammatic (visual) representations of how providers see their technology being used and how end users would actually use it in the field; allowing for a more user centered approach to the design process. For CBRN events usability is critical as sub-optimum design of technology could add to a responders’ workload in what is already a chaotic, ambiguous and safety critical environment.Keywords: AcciMap, CBRN, ergonomics, hierarchical task analysis, human factors
Procedia PDF Downloads 2258742 Understanding Cyber Kill Chains: Optimal Allocation of Monitoring Resources Using Cooperative Game Theory
Authors: Roy. H. A. Lindelauf
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Cyberattacks are complex processes consisting of multiple interwoven tasks conducted by a set of agents. Interdictions and defenses against such attacks often rely on cyber kill chain (CKC) models. A CKC is a framework that tries to capture the actions taken by a cyber attacker. There exists a growing body of literature on CKCs. Most of this work either a) describes the CKC with respect to one or more specific cyberattacks or b) discusses the tools and technologies used by the attacker at each stage of the CKC. Defenders, facing scarce resources, have to decide where to allocate their resources given the CKC and partial knowledge on the tools and techniques attackers use. In this presentation CKCs are analyzed through the lens of covert projects, i.e., interrelated tasks that have to be conducted by agents (human and/or computer) with the aim of going undetected. Various aspects of covert project models have been studied abundantly in the operations research and game theory domain, think of resource-limited interdiction actions that maximally delay completion times of a weapons project for instance. This presentation has investigated both cooperative and non-cooperative game theoretic covert project models and elucidated their relation to CKC modelling. To view a CKC as a covert project each step in the CKC is broken down into tasks and there are players of which each one is capable of executing a subset of the tasks. Additionally, task inter-dependencies are represented by a schedule. Using multi-glove cooperative games it is shown how a defender can optimize the allocation of his scarce resources (what, where and how to monitor) against an attacker scheduling a CKC. This study presents and compares several cooperative game theoretic solution concepts as metrics for assigning resources to the monitoring of agents.Keywords: cyber defense, cyber kill chain, game theory, information warfare techniques
Procedia PDF Downloads 1448741 Expression Level of Dehydration-Responsive Element Binding/DREB Gene of Some Local Corn Cultivars from Kisar Island-Maluku Indonesia Using Quantitative Real-Time PCR
Authors: Hermalina Sinay, Estri L. Arumingtyas
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The research objective was to determine the expression level of dehydration responsive element binding/DREB gene of local corn cultivars from Kisar Island Maluku. The study design was a randomized block design with single factor consist of six local corn cultivars obtained from farmers in Kisar Island and one reference varieties wich has been released by the government as a drought-tolerant varieties and obtained from Cereal Crops Research Institute (ICERI) Maros South Sulawesi. Leaf samples were taken is the second leaf after the flag leaf at the 65 days after planting. Isolation of total RNA from leaf samples was carried out according to the protocols of the R & A-BlueTM Total RNA Extraction Kit and was used as a template for cDNA synthesis. The making of cDNA from total RNA was carried out according to the protocol of One-Step Reverse Transcriptase PCR Premix Kit. Real Time-PCR was performed on cDNA from reverse transcription followed the procedures of Real MODTM Green Real-Time PCR Master Mix Kit. Data obtained from the real time-PCR results were analyzed using relative quantification method based on the critical point / Cycle Threshold (CP / CT). The results of gene expression analysis of DREB gene showed that the expression level of the gene was highest obtained at Deep Yellow local corn cultivar, and the lowest one was obtained at the Rubby Brown Cob cultivar. It can be concluded that the expression level of DREB gene of Deep Yellow local corn cultivar was highest than other local corn cultivars and Srikandi variety as a reference variety.Keywords: expression, level, DREB gene, local corn cultivars, Kisar Island, Maluku
Procedia PDF Downloads 3028740 Effect of Various Durations of Type 2 Diabetes on Muscle Performance
Authors: Santosh Kumar Yadav, Shobha Keswani, Nishat Quddus, Sohrab Ahmad Khan, Zuheb Ahmad Shiddiqui, Varsha Chorsiya
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Introduction: Early onset diabetes is more aggressive than the late onset diabetes. Diabetic individual has a greater spectrum of life period to suffer from its damage, complications, and long-term disability. This study aimed at assessing knee joint muscle performance under various durations of diabetes. Method and Materials: A total of 30 diabetic subjects (18 male and 12 females) without diabetic neuropathy were included for the study. They were divided into three groups with 5 years, 10 years and 15 years of duration of disease each. Muscle performance was evaluated through strength and flexibility. Peak torque for quadriceps muscle was measured using isokinetic dynamometer. Flexibility for quadriceps and hamstring muscles were measured through Ducan’s Elys test and 90/90 test. Results: The result showed significant difference in muscle strength (p<0.05), flexibility (p≤0.05) between groups. Discussion: Optimal muscle strength and flexibility are vital for musculoskeletal health and functional independence. Conclusion: The reduced muscle performance and functional impairment in nonneuropathic diabetic patients suggest that other mechanism besides neuropathy that contribute to altered biomechanics. These findings of this study project early management of these altered parameters through disease-specific physical therapy and assessment-based intervention. Clinical Relevance: Managing disability is more costly than managing disease. Prompt and timely identification and management strategy can dramatically reduce the cost of care for diabetic patients.Keywords: muscle flexibility, muscle performance, muscle torque, type 2 diabetes
Procedia PDF Downloads 3318739 Love Crystallized: The Significance of Divine Love Contemplation on Meaning and Purpose in Life in Islamic Psychology
Authors: Nur Farizah Binte Mohd Sedek
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Divine love is ubiquitous in many religions and philosophies. In the Islamic Sufi tradition, it is recognized as an “intense yearning for unification” with God. Previous literature demonstrates that divine love plays a role in forming meaning and purpose in one’s life. However, previous research has not explored the effects of the Islamic practice of divine love contemplation on meaning and purpose in life. The current study used an experimental design to investigate whether a divine love contemplation intervention has an impact on meaning and purpose in life in Muslims through the framework of Islamic Psychology. The sample consisted of 34 participants (7 males and 27 females) who were randomly assigned to one of two groups: Intervention (n = 20) and Control (n = 14). Participants in the intervention group did a general litany and a divine love supplication and contemplation exercise, while participants in the control group did only a general litany exercise. Three hypotheses were tested using a mixed-design two-way (split-plot) Analysis of Variance (ANOVA) to determine whether participants in the intervention group will report a significant increase in 1) divine love, 2) meaning in life, and 3) purpose in life from before to after the intervention, whereas participants in the control group will not report a significant change in the mentioned constructs. The results supported Hypothesis 1, in that a significant interaction between group and time emerged for divine love. Specifically, the intervention group reported a significant increase in divine love from before to after the intervention, whereas the control group did not report a significant change in divine love. Furthermore, the effect size was large, even though the mean difference was negligible, indicating that this change was substantial enough to have a considerable effect on the sample. However, the tests of the second and third hypotheses were not significant, suggesting that the divine love contemplation intervention did not have a significant impact on meaning or purpose in life. Suggestions for future research include qualitative phenomenological studies that could be conducted to glean experiential insight into the constructs from the participants’ individual accounts.Keywords: divine love, meaning in life, purpose in life, contemplation, islamic psychology
Procedia PDF Downloads 608738 The Effects of Cost-Sharing Contracts on the Costs and Operations of E-Commerce Supply Chains
Authors: Sahani Rathnasiri, Pritee Ray, Sardar M. N. Isalm, Carlos A. Vega-Mejia
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This study develops a cooperative game theory-based cost-sharing contract model for a business to consumer (B2C) e-commerce supply chain to minimize the overall supply chain costs and the individual costs within an information asymmetry scenario. The objective of this study is to address the issues of strategic interactions among the key players of the e-commerce supply chain operation, which impedes the optimal operational outcomes. Game theory has been included in the field of supply chain management to resolve strategic decision-making issues; however, most of the studies are limited only to two-echelons of the supply chains. Multi-echelon supply chain optimizations based on game-theoretic models are less explored in the previous literature. This study adopts a cooperative game model to focus on the common payoff of operations and addresses the issues of information asymmetry and coordination of a three-echelon e-commerce supply chain. The cost-sharing contract model integrates operational features such as production, inventory management and distribution with the contract related constraints. The outcomes of the model highlight the importance of maintaining lower operational costs by all players to obtain benefits from the cost-sharing contract. Further, the cost-sharing contract ensures true cost revelation, and hence eliminates the information asymmetry issues among the players. Comparing the results of the contract model with the de-centralized e-commerce supply chain operation further emphasizes that the cost-sharing contract derives Pareto-improved outcomes and minimizes the costs of overall e-commerce supply chain operation.Keywords: cooperative game theory, cost-sharing contract, e-commerce supply chain, information asymmetry
Procedia PDF Downloads 1318737 Real-Time Radar Tracking Based on Nonlinear Kalman Filter
Authors: Milca F. Coelho, K. Bousson, Kawser Ahmed
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To accurately track an aerospace vehicle in a time-critical situation and in a highly nonlinear environment, is one of the strongest interests within the aerospace community. The tracking is achieved by estimating accurately the state of a moving target, which is composed of a set of variables that can provide a complete status of the system at a given time. One of the main ingredients for a good estimation performance is the use of efficient estimation algorithms. A well-known framework is the Kalman filtering methods, designed for prediction and estimation problems. The success of the Kalman Filter (KF) in engineering applications is mostly due to the Extended Kalman Filter (EKF), which is based on local linearization. Besides its popularity, the EKF presents several limitations. To address these limitations and as a possible solution to tracking problems, this paper proposes the use of the Ensemble Kalman Filter (EnKF). Although the EnKF is being extensively used in the context of weather forecasting and it is being recognized for producing accurate and computationally effective estimation on systems with a very high dimension, it is almost unknown by the tracking community. The EnKF was initially proposed as an attempt to improve the error covariance calculation, which on the classic Kalman Filter is difficult to implement. Also, in the EnKF method the prediction and analysis error covariances have ensemble representations. These ensembles have sizes which limit the number of degrees of freedom, in a way that the filter error covariance calculations are a lot more practical for modest ensemble sizes. In this paper, a realistic simulation of a radar tracking was performed, where the EnKF was applied and compared with the Extended Kalman Filter. The results suggested that the EnKF is a promising tool for tracking applications, offering more advantages in terms of performance.Keywords: Kalman filter, nonlinear state estimation, optimal tracking, stochastic environment
Procedia PDF Downloads 1578736 De-Densifying Congested Cores of Cities and Their Emerging Design Opportunities
Authors: Faith Abdul Rasak Asharaf
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Every city has a threshold known as urban carrying capacity based on which it can withstand a particular density of people, above which the city might need to resort to measures like expanding its boundaries or growing vertically. As a result of this circumstance, the number of squatter communities is growing, as is the claustrophobic feeling of being confined inside a "concrete jungle." The expansion of suburbs, commercial areas, and industrial real estate in the areas surrounding medium-sized cities has resulted in changes to their landscapes and urban forms, as well as a systematic shift in their role in the urban hierarchy when functional endowment and connections to other territories are considered. The urban carrying capacity idea provides crucial guidance for city administrators and planners in better managing, designing, planning, constructing, and distributing urban resources to satisfy the huge demands of an evergrowing urban population. An ecological footprint is a criterion of urban carrying capacity, which is the amount of land required to provide humanity with renewable resources and absorb its trash. However, as each piece of land has its unique carrying capacity, including ecological, social, and economic considerations, these metropolitan areas begin to reach a saturation point over time. Various city models have been tried throughout the years to meet the increasing urban population density by moving the zones of work, life, and leisure to achieve maximum sustainable growth. The current scenario is that of a vertical city and compact city concept, in which the maximum density of people is attempted to fit into a definite area using efficient land use and a variety of other strategies, but this has proven to be a very unsustainable method of growth, as evidenced by the COVID-19 period. Due to a shortage of housing and basic infrastructure, densely populated cities gave rise to massive squatter communities, unable to accommodate the overflowing migrants. To achieve optimum carrying capacity, planning measures such as polycentric city and diffuse city concepts can be implemented, which will help to relieve the congested city core by relocating certain sectors of the town to the city periphery, which will help to create newer spaces for design in terms of public space, transportation, and housing, which is a major concern in the current scenario. The study's goal is focused on suggesting design options and solutions in terms of placemaking for better urban quality and urban life for the citizens once city centres have been de-densified based on urban carrying capacity and ecological footprint, taking the case of Kochi as an apt example of a highly densified city core, focusing on Edappally, which is an agglomeration of many urban factors.Keywords: urban carrying capacity, urbanization, urban sprawl, ecological footprint
Procedia PDF Downloads 838735 Antioxidative Maillard Reaction Products Derived from Gelatin Hydrolysate of Unicorn Leatherjacket Skin
Authors: Supatra Karnjanapratum, Soottawat Benjakul
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Gelatin hydrolysate, especially from marine resource, has been known to possess antioxidative activity. Nevertheless, the activity is still lower in comparison with the commercially available antioxidant. Maillard reactions can be use to increase antioxidative activity of gelatin hydrolysate, in which the numerous amino group could be involved in glycation. In the present study, gelatin hydrolysate (GH) from unicorn leatherjacket skin prepared using glycyl endopeptidase with prior autolysis assisted process was used for preparation of Maillard reaction products (MRPs) under dry condition. The impacts of different factors including, types of saccharides, GH to saccharide ratio, incubation temperatures, relative humidity (RH) and times on antioxidative activity of MRPs were investigated. MRPs prepared using the mixture of GH and galactose showed the highest antioxidative activity as determined by both ABTS radical scavenging activity and ferric reducing antioxidant power during heating (0-48 h) at 60 °C with 65% RH, compared with those derived from other saccharide tested. GH to galactose ratio at 2:1 (w/w) yielded the MRPs with the highest antioxidative activity, followed by the ratios of 1:1 and 1:2, respectively. When the effects of incubation temperatures (50, 60, 70 °C) and RH (55, 65, 75%) were examined, the highest browning index and the absorbance at 280 nm were found at 70 °C, regardless of RH. The pH and free amino group content of MRPs were decreased with the concomitant increase in antioxidative activity as the reaction time increased. Antioxidative activity of MRPs generally increased with increasing temperature and the highest antioxidative activity was found when RH of 55% was used. Based on electrophoresis of MRP, the polymerization along with the formation of high molecular weight material was observed. The optimal condition for preparing antioxidative MRPs was heating the mixture of GH and galactose (2:1) at 70 °C and 55% RH for 36 h. Therefore, antioxidative activity of GH was improved by Maillard reaction and the resulting MRP could be used as natural antioxidant in food products.Keywords: antioxidative activity, gelatin hydrolysate, maillard reaction, unicorn leatherjacket
Procedia PDF Downloads 2518734 Urban Security and Social Sustainability in Cities of Developing Countries
Authors: Taimaz Larimian, Negin Sadeghi
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Very little is known about the impacts of urban security on the level of social sustainability within the cities of developing countries. Urban security is still struggling to find its position in the social sustainability agenda, despite the significant role of safety and security on different aspects of peoples’ lives. This paper argues that urban safety and security should be better integrated within the social sustainability framework. With this aim, this study investigates the hypothesized relationship between social sustainability and Crime Prevention through Environmental Design (CPTED) approach at the neighborhood scale. This study proposes a model of key influential dimensions of CPTED analyzed into localized factors and sub-factors. These factors are then prioritized using pairwise comparison logic and fuzzy group Analytic Hierarchy Process (AHP) method in order to determine the relative importance of each factor on achieving social sustainability. The proposed model then investigates social sustainability in six case study neighborhoods of Isfahan city based on residents’ perceptions of safety within their neighborhood. Mixed method of data collection is used by using a self-administered questionnaire to explore the residents’ perceptions of social sustainability in their area of residency followed by an on-site observation to measure the CPTED construct. In all, 150 respondents from selected neighborhoods were involved in this research. The model indicates that CPTED approach has a significant direct influence on increasing social sustainability in neighborhood scale. According to the findings, among different dimensions of CPTED, ‘activity support’ and ‘image/ management’ have the most influence on people’s feeling of safety within studied areas. This model represents a useful designing tool in achieving urban safety and security during the development of more socially sustainable and user-friendly urban areas.Keywords: crime prevention through environmental design (CPTED), developing countries, fuzzy analytic hierarchy process (FAHP), social sustainability
Procedia PDF Downloads 3118733 Performance Based Seismic Retrofit of Masonry Infiled Reinforced Concrete Frames Using Passive Energy Dissipation Devices
Authors: Alok Madan, Arshad K. Hashmi
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The paper presents a plastic analysis procedure based on the energy balance concept for performance based seismic retrofit of multi-story multi-bay masonry infilled reinforced concrete (R/C) frames with a ‘soft’ ground story using passive energy dissipation (PED) devices with the objective of achieving a target performance level of the retrofitted R/C frame for a given seismic hazard level at the building site. The proposed energy based plastic analysis procedure was employed for developing performance based design (PBD) formulations for PED devices for a simulated application in seismic retrofit of existing frame structures designed in compliance with the prevalent standard codes of practice. The PBD formulations developed for PED devices were implemented for simulated seismic retrofit of a representative code-compliant masonry infilled R/C frame with a ‘soft’ ground story using friction dampers as the PED device. Non-linear dynamic analyses of the retrofitted masonry infilled R/C frames is performed to investigate the efficacy and accuracy of the proposed energy based plastic analysis procedure in achieving the target performance level under design level earthquakes. Results of non-linear dynamic analyses demonstrate that the maximum inter-story drifts in the masonry infilled R/C frames with a ‘soft’ ground story that is retrofitted with the friction dampers designed using the proposed PBD formulations are controlled within the target drifts under near-field as well far-field earthquakes.Keywords: energy methods, masonry infilled frame, near-field earthquakes, seismic protection, supplemental damping devices
Procedia PDF Downloads 3008732 Building an Arithmetic Model to Assess Visual Consistency in Townscape
Authors: Dheyaa Hussein, Peter Armstrong
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The phenomenon of visual disorder is prominent in contemporary townscapes. This paper provides a theoretical framework for the assessment of visual consistency in townscape in order to achieve more favourable outcomes for users. In this paper, visual consistency refers to the amount of similarity between adjacent components of townscape. The paper investigates parameters which relate to visual consistency in townscape, explores the relationships between them and highlights their significance. The paper uses arithmetic methods from outside the domain of urban design to enable the establishment of an objective approach of assessment which considers subjective indicators including users’ preferences. These methods involve the standard of deviation, colour distance and the distance between points. The paper identifies urban space as a key representative of the visual parameters of townscape. It focuses on its two components, geometry and colour in the evaluation of the visual consistency of townscape. Accordingly, this article proposes four measurements. The first quantifies the number of vertices, which are points in the three-dimensional space that are connected, by lines, to represent the appearance of elements. The second evaluates the visual surroundings of urban space through assessing the location of their vertices. The last two measurements calculate the visual similarity in both vertices and colour in townscape by the calculation of their variation using methods including standard of deviation and colour difference. The proposed quantitative assessment is based on users’ preferences towards these measurements. The paper offers a theoretical basis for a practical tool which can alter the current understanding of architectural form and its application in urban space. This tool is currently under development. The proposed method underpins expert subjective assessment and permits the establishment of a unified framework which adds to creativity by the achievement of a higher level of consistency and satisfaction among the citizens of evolving townscapes.Keywords: townscape, urban design, visual assessment, visual consistency
Procedia PDF Downloads 3158731 Soil Reinforcement by Stone Columns
Authors: Saou Mohamed Amine
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The construction industry has been identified as a user of substantial amount of materials and energy resources that has an enormous impact on environment. The energy efficient in refurbishment project is being considered as one of the approaches to achieve sustainability in construction industry. The increasing concern for environment has made building owners and designers to incorporate the energy efficiency features into their building projects.Keywords: construction industry, design team attributes, energy efficient performance, refurbishment projects characteristics
Procedia PDF Downloads 4368730 Recycling of End of Life Concrete Based on C2CA Method
Authors: Somayeh Lotfi, Manuel Eggimann, Eckhard Wagner, Radosław Mróz, Jan Deja
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One of the main environmental challenges in the construction industry is a strong social force to decrease the bulk transport of the building materials in urban environments. Considering this fact, applying more in-situ recycling technologies for Construction and Demolition Waste (CDW) is an urgent need. The European C2CA project develops a novel concrete recycling technology that can be performed purely mechanically and in situ. The technology consists of a combination of smart demolition, gentle grinding of the crushed concrete in an autogenous mill, and a novel dry classification technology called ADR to remove the fines. The feasibility of this recycling process was examined in demonstration projects involving in total 20,000 tons of End of Life (EOL) concrete from two office towers in Groningen, The Netherlands. This paper concentrates on the second demonstration project of C2CA, where EOL concrete was recycled on an industrial site. After recycling, the properties of the produced Recycled Aggregate (RA) were investigated, and results are presented. An experimental study was carried out on mechanical and durability properties of produced Recycled Aggregate Concrete (RAC) compared to those of the Natural Aggregate Concrete (NAC). The aim was to understand the importance of RA substitution, w/c ratio and type of cement to the properties of RAC. In this regard, two series of reference concrete with strength classes of C25/30 and C45/55 were produced using natural coarse aggregates (rounded and crushed) and natural sand. The RAC series were created by replacing parts of the natural aggregate, resulting in series of concrete with 0%, 20%, 50% and 100% of RA. Results show that the concrete mix design and type of cement have a decisive effect on the properties of RAC. On the other hand, the substitution of RA even at a high percentage replacement level has a minor and manageable impact on the performance of RAC. This result is a good indication towards the feasibility of using RA in structural concrete by modifying the mix design and using a proper type of cement.Keywords: C2CA, ADR, concrete recycling, recycled aggregate, durability
Procedia PDF Downloads 3948729 The Effectiveness of Using Picture Storybooks on Young English as a Foreign Language Learners for English Vocabulary Acquisition and Moral Education: A Case Study
Authors: Tiffany Yung Hsuan Ma
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The Whole Language Approach, which gained prominence in the 1980s, and the increasing emphasis on multimodal resources in educational research have elevated the utilization of picture books in English as a foreign language (EFL) instruction. This approach underscores real-world language application, providing EFL learners with a range of sensory stimuli, including visual elements. Additionally, the substantial impact of picture books on fostering prosocial behaviors in children has garnered recognition. These narratives offer opportunities to impart essential values such as kindness, fairness, and respect. Examining how picture books enhance vocabulary acquisition can offer valuable insights for educators in devising engaging language activities conducive to a positive learning environment. This research entails a case study involving two kindergarten-aged EFL learners and employs qualitative methods, including worksheets, observations, and interviews with parents. It centers on three pivotal inquiries: (1) The extent of young learners' acquisition of essential vocabulary, (2) The influence of these books on their behavior at home, and (3) Effective teaching strategies for the seamless integration of picture storybooks into EFL instruction for young learners. The findings can provide guidance to parents, educators, curriculum developers, and policymakers regarding the advantages and optimal approaches to incorporating picture books into language instruction. Ultimately, this research has the potential to enhance English language learning outcomes and promote moral education within the Taiwanese EFL context.Keywords: EFL, vocabulary acquisition, young learners, picture book, moral education
Procedia PDF Downloads 778728 Design and Analysis of Hybrid Morphing Smart Wing for Unmanned Aerial Vehicles
Authors: Chetan Gupta, Ramesh Gupta
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Unmanned aerial vehicles, of all sizes, are prime targets of the wing morphing concept as their lightweight structures demand high aerodynamic stability while traversing unsteady atmospheric conditions. In this research study, a hybrid morphing technology is developed to aid the trailing edge of the aircraft wing to alter its camber as a monolithic element rather than functioning as conventional appendages like flaps. Kinematic tailoring, actuation techniques involving shape memory alloys (SMA), piezoelectrics – individually fall short of providing a simplistic solution to the conundrum of morphing aircraft wings. On the other hand, the feature of negligible hysteresis while actuating using compliant mechanisms has shown higher levels of applicability and deliverability in morphing wings of even large aircrafts. This research paper delves into designing a wing section model with a periodic, multi-stable compliant structure requiring lower orders of topological optimization. The design is sub-divided into three smaller domains with external hyperelastic connections to achieve deflections ranging from -15° to +15° at the trailing edge of the wing. To facilitate this functioning, a hybrid actuation system by combining the larger bandwidth feature of piezoelectric macro-fibre composites and relatively higher work densities of shape memory alloy wires are used. Finite element analysis is applied to optimize piezoelectric actuation of the internal compliant structure. A coupled fluid-surface interaction analysis is conducted on the wing section during morphing to study the development of the velocity boundary layer at low Reynold’s numbers of airflow.Keywords: compliant mechanism, hybrid morphing, piezoelectrics, shape memory alloys
Procedia PDF Downloads 3148727 Optimization and Validation for Determination of VOCs from Lime Fruit Citrus aurantifolia (Christm.) with and without California Red Scale Aonidiella aurantii (Maskell) Infested by Using HS-SPME-GC-FID/MS
Authors: K. Mohammed, M. Agarwal, J. Mewman, Y. Ren
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An optimum technic has been developed for extracting volatile organic compounds which contribute to the aroma of lime fruit (Citrus aurantifolia). The volatile organic compounds of healthy and infested lime fruit with California red scale Aonidiella aurantii were characterized using headspace solid phase microextraction (HS-SPME) combined with gas chromatography (GC) coupled flame ionization detection (FID) and gas chromatography with mass spectrometry (GC-MS) as a very simple, efficient and nondestructive extraction method. A three-phase 50/30 μm PDV/DVB/CAR fibre was used for the extraction process. The optimal sealing and fibre exposure time for volatiles reaching equilibrium from whole lime fruit in the headspace of the chamber was 16 and 4 hours respectively. 5 min was selected as desorption time of the three-phase fibre. Herbivorous activity induces indirect plant defenses, as the emission of herbivorous-induced plant volatiles (HIPVs), which could be used by natural enemies for host location. GC-MS analysis showed qualitative differences among volatiles emitted by infested and healthy lime fruit. The GC-MS analysis allowed the initial identification of 18 compounds, with similarities higher than 85%, in accordance with the NIST mass spectral library. One of these were increased by A. aurantii infestation, D-limonene, and three were decreased, Undecane, α-Farnesene and 7-epi-α-selinene. From an applied point of view, the application of the above-mentioned VOCs may help boost the efficiency of biocontrol programs and natural enemies’ production techniques.Keywords: lime fruit, Citrus aurantifolia, California red scale, Aonidiella aurantii, VOCs, HS-SPME/GC-FID-MS
Procedia PDF Downloads 2158726 Economic Policy Promoting Economically Rational Behavior of Start-Up Entrepreneurs in Georgia
Authors: Gulnaz Erkomaishvili
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Introduction: The pandemic and the current economic crisis have created problems for entrepreneurship and, therefore for start-up entrepreneurs. The paper presents the challenges of start-up entrepreneurs in Georgia in the time of pandemic and the analysis of the state economic policy measures. Despite many problems, the study found that in 54.2% of start-ups surveyed under the pandemic, innovation opportunities were growing. It can be stated that the pandemic was a good opportunity to increase the innovative capacity of the enterprise. 52% of the surveyed start-up entrepreneurs managed to adapt to the current situation and increase the sale of their products/services through remote channels. As for the assessment of state support measures by start-up entrepreneurs, a large number of Georgian start-ups do not assess the measures implemented by the state positively. Methodology: The research process uses methods of analysis and synthesis, quantitative and qualitative, interview/survey, grouping, relative and average values, graphing, comparison, data analysis, and others. Main Findings: Studies have shown that for the start-up entrepreneurs, the main problem remains: inaccessible funding, workers' qualifications gap, inflation, taxes, regulation, political instability, inadequate provision of infrastructure, amount of taxes, and other factors. Conclusions: The state should take the following measures to support business start-ups: create an attractive environment for investment, availability of soft loans, creation of an insurance system, infrastructure development, increase the effectiveness of tax policy (simplicity of the tax system, clarity, optimal tax level ); promote export growth (develop strategy for opening up international markets, build up a broad marketing network, etc.).Keywords: start-up entrepreneurs, startups, start-up entrepreneurs support programs, start-up entrepreneurs support economic policy
Procedia PDF Downloads 1198725 Development of National Education Policy-2020 Aligned Student-Centric-Outcome-Based-Curriculum of Engineering Programmes of Polytechnics in India: Faculty Preparedness and Challenges Ahead
Authors: Jagannath P. Tegar
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The new National Education Policy (NEP) 2020 of Govt. of India has envisaged a major overhaul of the education system of India, in particular, the revamping of the Curriculum of Higher Education. In this process, the faculty members of the Indian universities and institutions have a challenging role in developing the curriculum, which is a shift from the traditional (content-based) curriculum to a student-centric- outcome-based Curriculum (SC-OBC) to be implemented in all of the Universities and institutions. The efforts and initiatives on the design and implementation of SC-OBC are remarkable in the engineering and technical education landscape of the country, but it is still in its early stages and many more steps are needed for the successful adaptation in every level of Higher Education. The premier institute of Govt. of India (NITTTR, Bhopal) has trained and developed the capacity and capability among the teachers of Polytechnics on the design and development of Student Centric - Outcome Based Curriculum and also providing academic consultancy for reforming curriculum in line of NEP- 2020 envisions for the states such as Chhattisgarh, Bihar and Maharashtra to make them responsibly ready for such a new shift in Higher Education. This research-based paper is on three main aspects: 1) the level of acceptance and preparedness of teachers /faculty towards NEP-2020 and student-centred outcome-based learning. 2) the extent of implementing NEP-2020 and student-centered outcome-based learning at Indian institutions/ universities and 3) the challenges of implementing NEP-2020 and student-centered outcome-based learning outcome-based education in the Indian context. The paper content will inspire curriculum designers and developers to prepare SC-OBC that meets the specific needs of industry and society at large, which is intended in the NEP-2020 of Govt. of IndiaKeywords: outcome based curriculum, student centric learning, national education policy -2020, implementation of nep-2020. outcome based learning, higher education curriculum
Procedia PDF Downloads 848724 Neural Network based Risk Detection for Dyslexia and Dysgraphia in Sinhala Language Speaking Children
Authors: Budhvin T. Withana, Sulochana Rupasinghe
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The educational system faces a significant concern with regards to Dyslexia and Dysgraphia, which are learning disabilities impacting reading and writing abilities. This is particularly challenging for children who speak the Sinhala language due to its complexity and uniqueness. Commonly used methods to detect the risk of Dyslexia and Dysgraphia rely on subjective assessments, leading to limited coverage and time-consuming processes. Consequently, delays in diagnoses and missed opportunities for early intervention can occur. To address this issue, the project developed a hybrid model that incorporates various deep learning techniques to detect the risk of Dyslexia and Dysgraphia. Specifically, Resnet50, VGG16, and YOLOv8 models were integrated to identify handwriting issues. The outputs of these models were then combined with other input data and fed into an MLP model. Hyperparameters of the MLP model were fine-tuned using Grid Search CV, enabling the identification of optimal values for the model. This approach proved to be highly effective in accurately predicting the risk of Dyslexia and Dysgraphia, providing a valuable tool for early detection and intervention. The Resnet50 model exhibited a training accuracy of 0.9804 and a validation accuracy of 0.9653. The VGG16 model achieved a training accuracy of 0.9991 and a validation accuracy of 0.9891. The MLP model demonstrated impressive results with a training accuracy of 0.99918, a testing accuracy of 0.99223, and a loss of 0.01371. These outcomes showcase the high accuracy achieved by the proposed hybrid model in predicting the risk of Dyslexia and Dysgraphia.Keywords: neural networks, risk detection system, dyslexia, dysgraphia, deep learning, learning disabilities, data science
Procedia PDF Downloads 708723 A Sociological Investigation on the Population and Public Spaces of Nguyen Cong Tru, a Soviet-Style Collective Housing Complex in Hanoi in Regards to Its New Community-Focused Architectural Design
Authors: Duy Nguyen Do, Bart Julien Dewancker
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Many Soviet-style collective housing complexes (also known as KTT) were built since the 1960s in Hanoi to support the post-war population growth. Those low-rise buildings have created well-knitted, robust communities, so much to the point that in most complexes, all families in one housing block would know each other, occasionally interact and provide supports in need. To understand how the community of collective housing complexes have developed and maintained in order to adapt their advantages into modern housing designs, the study is executed on the site of Nguyen Cong Tru KTT. This is one of the oldest KTT in Hanoi, completed in 1954. The complex also has an unique characteristic that is closely related to its community: the symbiotic relationship with Hom – a flea market that has been co-developing with Nguyen Cong Tru KTT since its beginning. The research consists of three phases: the first phase is a sociological investigation with Nguyen Cong Tru KTT’s current residents and a site survey on the complex’s economic and architectural characteristics. In the second phase, the collected data is analyzed to find out people’s opinions with the KTT’s concerning their satisfaction with the current housing status, floor plan organization, community, the relationship between the KTT’s dedicated public spaces with the flea market and their usage. Simultaneously, the master plan and gathered information regarding current architectural characteristics of the complex are also inspected. On the third phase, the analyses’ results will provide information regarding the issues, positive trends and significant historical features of the complex’s architecture in order to generate suitable proposals for the redesigning project of Nguyen Cong Tru KTT, a design focused on vitalizing modern apartments’ communities.Keywords: collective house community, collective house public space, community-focused, redesigning Nguyen Cong Tru KTT, sociological investigation
Procedia PDF Downloads 3688722 Influence of Stress Relaxation and Hysteresis Effect for Pressure Garment Design
Authors: Chia-Wen Yeh, Ting-Sheng Lin, Chih-Han Chang
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Pressure garment has been used to prevent and treat the hypertrophic scars following serious burns since 1970s. The use of pressure garment is believed to hasten the maturation process and decrease the highness of scars. Pressure garment is custom made by reducing circumferential measurement of the patient by 10%~20%, called Reduction Factor. However the exact reducing value used depends on the subjective judgment of the therapist and the feeling of patients throughout the try and error process. The Laplace Law can be applied to calculate the pressure from the dimension of the pressure garment by the circumferential measurements of the patients and the tension profile of the fabrics. The tension profile currently obtained neglects the stress relaxation and hysteresis effect within most elastic fabrics. The purpose of this study was to investigate the influence of the tension attenuation, from stress relaxation and hysteresis effect of the fabrics. Samples of pressure garment were obtained from Sunshine Foundation Organization, a nonprofit organization for burn patients in Taiwan. The wall tension profile of pressure garments were measured on a material testing system. Specimens were extended to 10% of the original length, held for 1 hour for the influence of the stress relaxation effect to take place. Then, specimens were extended to 15% of the original length for 10 seconds, then reduced to 10% to simulate donning movement for the influence of the hysteresis effect to take place. The load history was recorded. The stress relaxation effect is obvious from the load curves. The wall tension is decreased by 8.5%~10% after 60mins of holding. The hysteresis effect is obvious from the load curves. The wall tension is increased slightly, then decreased by 1.5%~2.5% and lower than stress relaxation results after 60mins of holding. The wall tension attenuation of the fabric exists due to stress relaxation and hysteresis effect. The influence of hysteresis is more than stress relaxation. These effect should be considered in order to design and evaluate the pressure of pressure garment more accurately.Keywords: hypertrophic scars, hysteresis, pressure garment, stress relaxation
Procedia PDF Downloads 5158721 Elucidation of Dynamics of Murine Double Minute 2 Shed Light on the Anti-cancer Drug Development
Authors: Nigar Kantarci Carsibasi
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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.Keywords: cancer, drug design, elastic network model, MDM2
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